Junctional amino acids determine the maturation pathway of an antibody
Junctional amino acids determine the maturation pathway of an antibody
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DOI：
10.1016/s1074-7613(00)80108-9
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发表时间：
1999-09-01
期刊：
影响因子：
32.4
通讯作者：
Azuma, T
中科院分区：
文献类型：
--
作者：
Furukawa, K;Akasako-Furukawa, A;Azuma, T
我们发现C57 BL/6小鼠对（4-羟基-3-硝基苯基）乙酰基的免疫反应中存在两种不同的抗体成熟途径，并且远早于体细胞超突变的过程引入的连接氨基酸决定了亲和力成熟的途径。属于每个途径的抗体被清楚地分成两个独立的分支。我们还通过将抗体的结合常数作为第三轴引入到基因树中，构建了抗体进化的三维适应度景观，使我们能够理解连接多样性在抗体“进化性”中的意义。抗原-抗体相互作用的热力学分析表明，抗原结合位点的高构象多样性允许增强抗体的进化性。
We found that two distinct antibody maturation pathways exist in the immune response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl and that the junctional amino acid introduced by a process far preceding somatic hypermutation determined the pathway of affinity maturation. Antibodies belonging to each pathway clearly separated into two separate branches of a phylogenic tree. We also constructed a three-dimensional fitness landscape for antibody evolution by introducing the association constants of the antibodies into the phylogenic tree as the third axis, allowing us to comprehend the significance of junctional diversity in the "evolvability" of antibodies. Thermodynamic analyses of the antigen-antibody interactions suggested that a high conformational versatility in the antigen-combining site allows for the enhanced evolvability of antibodies.